Cerebrovascular disease and strokes are a major cause of morbidity and mortality throughout the world. Strokes may develop as a complication of hypertension or other cardiovascular disorders, or may be caused by diseases of parenchymal brain blood vessels and disturbances in local cerebral blood flow. The neurotransmitter, serotonin and norepinephrine have been detected (by histochemistry) in the walls of cerebral blood vessels where they have been implicated in the regulation of intraparenchymal blood flow. Both substances are vasoactive and cause blood vessels to contract when applied locally. Very little is known about the synthesis, release and inactivation of these neurotransmitters within cerebral blood vessels. This poposal requests support to develop a program of research that will explore the biochemistry and pharmacology of vascular neurotransmitters within brain intraparenchymal blood vessels. Initial studies will utilize a recently perfected method for separating blood vessels from surrounding neuropil and will extend our studies on the control of serotonin levels within this brain fraction. Related studies will characterize the levels of other neurotransmitters (dopamine, norepinephrine, epinephrine, acetylcholine, and BABA) and their biosynthetic and degradative enzymes within isolated microvessels and will attempt to identify the loci of origin of the neurons that project onto these blood vessels. Pharmacological and morphological techniques will also be utilized. The proposed research may provide useful information about neurotransmission mechanisms regulating brain vascular tissue which may, in turn, underlie new strategies for the prophylaxis and treatment of cerebrovascular disease.